Gamma Delta T Cells in Acute Myeloid Leukemia: Biology and Emerging Therapeutic Strategies

Authors

Adishwar Rao
Akriti Agrawal
Gautam Borthakur
Venkata Lokesh Battula
Abhishek Maiti

Publication Date

2-27-2024

Journal

The Journal for ImmunoTherapy of Cancer

Abstract

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of relapse, enhanced graft-versus-leukemia effect, and decreased graft-versus-host disease in patients with AML who have higher reconstitution of γδ T cells following allogeneic hematopoietic stem cell transplantation. Clinical trials leveraging γδ T cell biology have used unmodified and modified allogeneic cells as well as bispecific engagers and monoclonal antibodies. In this review, we discuss γδ T cells' biology, roles in cancer and AML, and mechanisms of immune escape and antileukemia effect; we also discuss recent clinical advances related to γδ T cells in the field of AML therapeutics.

Keywords

Immunity, Cellular; Immunotherapy, Adoptive; Hematologic Neoplasms

DOI

10.1136/jitc-2023-007981

PMID

38417915

PMCID

PMC10900322

PubMedCentral® Posted Date

February 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes